Lipid Droplet-Targeted BODIPY–Hemicyanine Hybrid Fluorescent Probes for Real-Time Monitoring of pH and Viscosity

Lipid droplets (LDs) are pivotal organelles in lipid metabolism, whose dysfunction links to atherosclerosis and cancer. Microenvironmental factors, like microviscosity and pH, are closely linked to various pathophysiological processes. However, single-parameter diagnostic tools fall short of comprehensive assessments of diseases. To address this challenge, we have developed a novel multifunctional fluorescent probe series, LD-VP, by fusing a BODIPY core with hydroxyethyl-substituted hemicyanine moieties via an ethylene bond. These hybrids can selectively target LDs while detecting viscosity (via restricted molecular rotations to enhance red fluorescence) and pH (via disrupting the hemicyanine structure, causing blue-shifted emission under alkaline conditions). Notably, LD-VP1 can successfully discriminate tumor cells from normal cells and effectively reveals pathological LD features (increased quantity, size, and viscosity with stable pH) during atherosclerotic foam cell formation. This work successfully demonstrates the practical value of multifunctional probes for understanding and diagnosing complex diseases, offering a stellar example for the advancement of multifunctional probe development.